10-101514855-C-G

Variant names:

• chr10-101514855-C-G
• rs12769629
• NM_033637.4:c.325-6784C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033637.4(BTRC):​c.325-6784C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,170 control chromosomes in the GnomAD database, including 6,340 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (6340 hom., cov: 32)
• Consequence: BTRC NM_033637.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• Publications: 2 publications found

Genes affected

BTRC (HGNC:1144): (beta-transducin repeat containing E3 ubiquitin protein ligase) This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbws class; in addition to an F-box, this protein contains multiple WD-40 repeats. The encoded protein mediates degradation of CD4 via its interaction with HIV-1 Vpu. It has also been shown to ubiquitinate phosphorylated NFKBIA (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha), targeting it for degradation and thus activating nuclear factor kappa-B. Alternatively spliced transcript variants have been described. A related pseudogene exists in chromosome 6. [provided by RefSeq, Mar 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033637.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTRC	NM_033637.4	MANE Select	c.325-6784C>G		intron	N/A	NP_378663.1
	BTRC	NM_001256856.2		c.247-6784C>G		intron	N/A	NP_001243785.1
	BTRC	NM_003939.5		c.217-6784C>G		intron	N/A	NP_003930.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTRC	ENST00000370187.8	TSL:1 MANE Select	c.325-6784C>G		intron	N/A	ENSP00000359206.3
	BTRC	ENST00000393441.8	TSL:1	c.247-6784C>G		intron	N/A	ENSP00000377088.5
	BTRC	ENST00000408038.6	TSL:1	c.217-6784C>G		intron	N/A	ENSP00000385339.2

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40072 AN: 152052 Hom.: 6338 Cov.: 32

Gnomad AFR AF: 0.0853

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.269

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.263 AC: 40076 AN: 152170 Hom.: 6340 Cov.: 32 AF XY: 0.270 AC XY: 20050 AN XY: 74384

African (AFR) AF: 0.0851 AC: 3536 AN: 41532

American (AMR) AF: 0.296 AC: 4530 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 910 AN: 3470

East Asian (EAS) AF: 0.186 AC: 965 AN: 5180

South Asian (SAS) AF: 0.401 AC: 1932 AN: 4822

European-Finnish (FIN) AF: 0.392 AC: 4151 AN: 10580

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 22988 AN: 67980

Other (OTH) AF: 0.268 AC: 565 AN: 2110

Alfa AF: 0.174 Hom.: 399

Bravo AF: 0.247

Asia WGS AF: 0.324 AC: 1125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.1
DANN	Benign	0.79
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12769629; hg19: chr10-103274612;